Identifying chronic thromboembolic pulmonary hypertension through the French national hospital discharge database.

Chronic thromboembolic pulmonary hypertension (CTEPH), a rare pulmonary vascular disease, is often misdiagnosed due to nonspecific symptoms. The objective of the study was to develop, refine and validate a case ascertainment algorithm to identify CTEPH patients within the French exhaustive hospital discharge database (PMSI), and to use it to estimate the annual number of hospitalized patients with CTEPH in France in 2015, as a proxy for disease prevalence. As ICD-10 coding specifically for CTEPH was not available at the time of the study, a case ascertainment algorithm was developed in close collaboration with an expert committee, using a two-step process (refinement and validation), based on matched data from PMSI and hospital medical records from 2 centres. The best-performing algorithm (specificity 95%, sensitivity 70%) consisted of ≥1 pulmonary hypertension (PH) diagnosis during 2015 and any of the following criteria over 2009-2015: (i) CTEPH interventional procedure, (ii) admission for PH and pulmonary embolism (PE), (iii) PE followed by hospitalization in competence centre then in reference centre, (iv) history of PE and right heart catheterization. Patients with conditions suggestive of pulmonary arterial hypertension were excluded. A total of 3,138 patients hospitalized for CTEPH was estimated for 2015 (47 cases/million, range 43 to 50 cases/million). Assuming that patients are hospitalized at least once a year, the present study provides an estimate of the minimal prevalence of CTEPH and confirms the heavy burden of this disease.

Long-term morbidity, mortality, and economics of rheumatoid arthritis.

OBJECTIVE: To estimate the morbidity, mortality, and lifetime costs of care for rheumatoid arthritis (RA). METHODS: We developed a Markov model based on the Arthritis, Rheumatism, and Aging Medical Information System Post-Marketing Surveillance Program cohort, involving 4,258 consecutively enrolled RA patients who were followed up for 17,085 patient-years. Markov states of health were based on drug treatment and Health Assessment Questionnaire scores. Costs were based on resource utilization, and utilities were based on visual analog scale-based general health scores. RESULTS: The cohort had a mean age of 57 years, 76.4% were women, and the mean duration of disease was 11.8 years. Compared with a life expectancy of 22.0 years for the general population, this cohort had a life expectancy of 18.6 years and 11.3 quality-adjusted life years. Lifetime direct medical care costs were estimated to be $93,296. Higher costs were associated with higher disability scores. CONCLUSION: A Markov model can be used to estimate lifelong morbidity, mortality, and costs associated with RA, providing a context in which to consider the potential value of new therapies for the disease.

"Arthritis specific" global health analog scales assess "generic" health related quality-of-life in patients with rheumatoid arthritis.

OBJECTIVE: Quality-of-life assessment is receiving increased attention as an outcome measure in rheumatoid arthritis (RA). The most widely used instruments use variations on a vertical visual analog scale (VAS). Since the Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scales (AIMS), and other instruments have long included a "global" arthritis horizontal VAS (GLOB), we studied whether these 2 approaches assess the same concept. METHODS: We studied 663 patients with RA from 4 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers and had them complete, in different parts of the same HAQ, the GLOB and the Torrance "feeling thermometer" (FT). RESULTS: The 2 scales were highly correlated (r = -0.676; p < 0.001). Reliability (estimated by 6 month test-retest) was 0.62 for the FT and 0.83 for the GLOB. The GLOB correlated more strongly than the FT with disability (r = 0.561 vs -0.507) and pain (0.630 vs -0.553). In stepwise regressions, pain and then disability were the dominant predictors of both GLOB and FT, followed weakly by joint count and then other variables. Patients with greater disability placed more emphasis on pain and patients with greater pain appeared to value more the contribution of disability. Change scores over 6 months between GLOB and FT correlated very well (-0.59). CONCLUSION: "Health" and "health related quality-of-life" are nearly equivalent terms. Since large longitudinal rheumatology databases contain thousands of global health VAS values, data for longitudinal quality-of-life studies in arthritis are already available, and this dimension may readily be added to longterm outcome assessment. In patients with RA, "generic" and "disease specific" assessments yield very similar results.

Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy.

OBJECTIVE: Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug. METHODS: We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start. RESULTS: Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice.

Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study.

BACKGROUND: Gastrointestinal tract (GI) complications associated with nonsteroidal anti-inflammatory drug (NSAID) use are the most common serious adverse drug reactions in the United States. Nonsteroidal anti-inflammatory drugs cause both minor GI side effects such as abdominal pain and vomiting and serious GI events such as ulcers and bleeding. This study evaluates the event rates for all NSAID-induced GI complications in patients with rheumatoid arthritis, describes the time course of these events, and evaluates the role of prophylactic therapy with antacids and H2 receptor antagonists. METHODS: We studied 1921 patients with rheumatoid arthritis from 8 ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System) centers. Patients were selected for the study if they were treated with NSAIDs and had at least 2.5 years of observation available. Information on GI complications attributed to NSAIDs was obtained from validated patient self-reports collected every 6 months and supplemented by review of hospital records for all hospitalizations. RESULTS: Approximately 15% of the 1921 patients reported an NSAID-induced GI side effect during the 2.5 year observation period. Forty-two patients had a serious GI complication requiring hospitalization; 34 of these 42 patients did not have a preceding GI side effect. Patients who were taking antacids and H2 receptor antagonists did not have a significantly lower risk for serious GI complications than did those not taking such medications. Asymptomatic patients taking these medications had a significantly higher risk for GI complications compared with those who did not take these medications (standardized odds ratio, 2.14;95% confidence interval, 1.06-4.32). CONCLUSIONS: A large majority of patients with serious GI complications do not have preceding mild side effects. Prophylactic treatment with antacids and H2 receptor antagonists is of questionable value and may increase the risk for subsequent serious GI complications.

Comparative toxicity of non-steroidal anti-inflammatory agents.

Comparative toxicity of non-steroidal anti-inflammatory drugs was assessed using the Stanford Toxicity Index consisting of weighted symptoms, laboratory abnormalities and hospitalizations in 2976 consecutively enrolled rheumatoid arthritis patients from eight data bank centers with 27,936 patient-years of observation. Scores ranged from 1.77 (SE 0.20) for aspirin to 5.94 (SE 0.92) for meclofenamate, with many differences between drugs being 2- to 3-fold and highly statistically significant. Results are consistent with our prior data, persist when assessed by several different scoring algorithms, are consistent across data bank centers and are consistent with data of others. There are major and reproducible differences in the overall toxicity of different non-steroidal anti-inflammatory drugs.

A reevaluation of aspirin therapy in rheumatoid arthritis.

BACKGROUND: Aspirin therapy has been largely superseded by prescription nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid arthritis, in part because of premarketing studies suggesting lesser toxic effects for NSAIDs than for aspirin. This study evaluates these toxic effects in a postmarketing population of patients with rheumatoid arthritis. METHODS: We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eight Arthritis, Rheumatism, and Aging Medical Information System Post-marketing Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted for variable severity and severity of side effect. RESULTS: The toxicity index was only 1.37 (SE = 0.10) for aspirin and 1.87 to 2.90 for selected nonsalicylate NSAIDs. These differences were consistent across centers and remained after statistical adjustment for differing patient characteristics. There was a different toxicity with different aspirin preparations, with a score for plain aspirin of 1.36 (SE = 0.23), for buffered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparations of 0.92 (0.14). Most important, there were strong dose effects, with a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 2601 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspirin dose taken was only 2665 mg/d, approximately eight "tablets," compared with 3600 to 4800 mg/d used in the 16 pivotal premarketing studies reviewed. Average NSAID doses were, on the other hand, lower in premarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices). CONCLUSIONS: Aspirin therapy, in doses commonly employed in practice, has an excellent safety profile in rheumatoid arthritis, and it is the least costly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer management strategies for rheumatoid arthritis emphasize NSAID use as symptomatic therapy and use of disease-modifying anti-rheumatic drug therapy for anti-inflammatory objectives. Thus, the original recommendation for "anti-inflammatory" doses of aspirin now is less easily justified. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis.

The relative toxicity of alternative therapies for rheumatoid arthritis: implications for the therapeutic progression.

The traditional pyramid for the therapeutic progression in rheumatoid arthritis (RA) is based on assumptions that RA is a mild disease, that nonsteroidal antiinflammatory drugs (NSAIDs) have low toxicity, and that disease-modifying antirheumatic drugs (DMARDs) are extremely toxic. This article reviews data from ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), casting strong doubt on these assumptions. NSAIDs result in 1.3% excess gastrointestinal hospitalizations per year. Mortality rates in RA are far above those expected from age- and sex-matched populations. Individual NSAIDs show widely different overall quantitative toxicity indices, as do individual DMARDs. However, the ranges of toxicity of the two classes of drugs show nearly complete overlap. It is suggested that the new therapeutic progression in RA should emphasize initial use of DMARDs, beginning with the least toxic.

The health assessment questionnaire 1992: status and review.

Over 100 papers describing and utilizing the Stanford Health Assessment Questionnaire (HAQ) have been published since 1980. A brief overview of the HAQ is presented along with a guide to the accumulated literature. The topics covered include: studies using the disability, pain, economic, and drug side effect dimensions of the HAQ; reliability and validity studies; applications to various rheumatic diseases; language adaptations; modifications and derivative scales; studies correlating the HAQ with sociodemographic, health status, laboratory, and physical measures; and randomized controlled trials and observational studies using the HAQ. A few comments regarding future directions for research are also presented.

Rectal thiopental versus an intramuscular cocktail for sedating children before computerized tomography.

The sedative effects of rectal thiopental sodium and an intramuscular cocktail of meperidine hydrochloride, chlorpromazine hydrochloride and promethazine hydrochloride were compared in 72 pediatric patients undergoing computerized tomography (CT). Pediatric patients scheduled were randomly assigned to receive either the i.m. cocktail (2.0 mg/kg of meperidine, 1.0 mg/kg of both chlorpromazine and promethazine) or 25--45 mg/kg of thiopental rectally before scanning. Side effects, and onset, duration and depth of sedation were recorded by 14 unblinded investigators. Clarity of CT scans was rated by two blinded radiologists. Additional doses of sedatives were administered as necessary. Sedation was not achieved in 3% of the thiopental group or in 14+ of the i.m. cocktail group. Additional sedatives were required by eight patients in the thiopental group and by five patients in the cocktail group. The mean time for onset of sedation was 8 minutes with thiopental and 18 minutes with the cocktail. The mean duration of sedation was 7 hours for the cocktail group and 2.75 hours for the 25-mg/kg rectal thiopental group. All scans were diagnostic (acceptable) in the rectal thiopental group, but 14% of those in the i.m. cocktail group were nondiagnostic. Rectal thiopental is an effective alternative to an i.m. cocktail for sedating children before CT scans and may reduce the number of nondiagnostic scans.

Rectal thiopental for sedation of children for computed tomography.

Rectally administered thiopental was evaluated for sedation in pediatric computed tomography and compared with "cardiac cocktail" sedation. The drug produced sedation as effective as the "cocktail" with easier administration, more rapid onset, and shorter duration of sedation. Although no complications were observed, careful observation for respiratory depression is suggested.